The Master RAD Protocol is a Phase I/II, multi-center, open-label trial of promising combination therapies for highly experience HIV-infected children with rapidly progressing or advanced disease for whom current therapy is failing. The Master RAD Protocol schema is designed to allow new therapeutic combinations to be studies as "rolling screens" through multiple generations of RAD Protocols (RAD-1, RAD-2, RAD-3, etc.). Each combination is studied "independently" rather than as a comparison to the other combinations. There may be a common "linking" regimen between any two RAD generations which could permit an indirect comparison of included therapies across generations. However, each RAD is an independent study and linking arms are not required. Real-time HIV RNA load will be assessed in each RAD Protocol and lack of initial reduction or loss of reduction is defined as the primary endpoint for the study. Initial viral load reduction is expected with each of the chosen combinations. The Master RAD Protocol is an intensive antiretroviral treatment algorithm in which additional aspects of pediatric HIV disease will be studies. Pharmacokinetic studies are necessary to fully characterize agents in pediatric populations. Central nervous system (CNS) sub-studies may be designed to enable a better understanding of how best to optimize therapy of subjects with HIV encephalopathy and to provide prophylaxis against this possibility in other children at risk. Intensive immunology studies may also be offered to define how best to effect immunologic reconstitution. Pertinent questions may also be asked within the context of the RAD Protocol as to how best to manage opportunistic infections in the populations with advanced disease. Virologic studies can be designed to answer selected questions with each RAD Protocol generation.